Epidemiology

Ependymomas its the third most common pediatric CNS tumor. Although as a group they represent less then 10% of all neuroepithelial tumors, ependymomas account for nearly one third of intracranial tumors in children younger than 3 years. The age distribution for ependymomas is bimodal; the first peak incidence occurs around age 5-6 years when infratentorial lesions predominate, and a second, later peak occurs in the third and fourth decades, at which time spinal examples are most common.

In general, most pediatric ependymomas are intracranial ependymomas, whereas well over one half of adult ependymomas are spinal cord ependymomas.

Ependymomas have double the rate of occurrence in white individuals compared with black individuals, whereas these tumors are equally distributed between the sexes. Although most ependymomas are sporadic, they may also be encountered in the context of neurofibromatosis type 2.

Ependymal tumors in adults are rare, accounting for less than 4 % of primary tumors of the central nervous system in adults.

Classification

Etiology

Fetal ependymal tanycytes directly give rise to mature ependymocytes, whereas other tanycytic populations mature and remain as ependymal tanycytes within selective regions of the ventricular system, particularly the hypothalamic region of the third ventricle and within circumventricular organs. Specialized ependyma of the circumventricular organs and choroid plexus cells are additional highly specialized ependymal cells that ultimately derive from this developmental pathway.

Genomics

The most substantial magnitude of differentially expressed genes (DEGs) in ependymoma might be HOX genes. However, whether the differential expression of these genes is the cause or consequence of the disease remains to be elucidated in a larger prospective study
1).

Loss of chromosome 22 and gain of 1q are the most frequent genomic aberrations in ependymomas, indicating that genes mapping to these regions are critical in their pathogenesis. Using real-time quantitative PCR, Karakoula et al. measured relative copy numbers of 10 genes mapping to 22q12.3-q13.33 and 10 genes at 1q21-32 in a series of 47 pediatric intracranial ependymomas. Loss of one or more of the genes on 22 was detected in 81% of cases, with RAC2 and C22ORF2 at 22q12-q13.1 being deleted most frequently in 38% and 32% of ependymoma samples, respectively. Combined analysis of quantitative-PCR with methylation-specific PCR and bisulphite sequencing revealed a high rate (>60% ependymoma) of transcriptional inactivation of C22ORF2, indicating its potential importance in the development of pediatric ependymomas. Increase of relative copy numbers of at least one gene on 1q were detected in 61% of cases, with TPR at 1q25 displaying relative copy number gains in 38% of cases. Patient age was identified as a significant adverse prognostic factor, as a significantly shorter overall survival time (P = 0.0056) was observed in patients <2 years of age compared with patients who were >2 years of age. Loss of RAC2 at 22q13 or amplification of TPR at 1q25 was significantly associated with shorter overall survival in these younger patients (P = 0.0492 and P = < 0.0001, respectively). This study identifies candidate target genes within 1q and 22q that are potentially important in the pathogenesis of intracranial pediatric ependymomas
2).

Clinical features

The nonspecific clinical presentation of a spinal cord tumor frequently results in delay of diagnosis with opposing outcomes.

Outcome

Ependymoma typically has a better overall survival rate than most gliomas.

Histopathological classification is not sufficient to show variable outcomes, and fails to show prognostic markers of the diverse outcomes; hence, it is essential to understand biological mechanisms.

These tumors have a distinct propensity for metastasis, both within and outside the CNS. However, dissemination at the time of first presentation and retrograde dissemination of the tumor is rare.

Case series

2015

176 ependymoma samples (World Health Organization grade II and III) were reviewed at Huashan Hospital. Both children and adults were included.

They performed multifactorial analyses of clinical prognostic factors and the biomolecular marker expressions of nucleolin, epidermal growth factor receptor (EGFR) and caveolae-associated protein caveolin 1 by immunohistochemistry. We identified the probabilities of progression-free survival and overall survival using univariate and multivariate statistical methods. The participants were diagnosed with ependymomas between 2002 and 2010, including distributions of tumor locations in intracranial and extracranial regions. Nucleolin was overexpressed in 67 % of our samples, demonstrating a subgroup with poor outcome; particularly infratentorial and anaplastic ependymomas. There was no significant correlation between the expression of EGFR and caveolin-1 and clinical outcomes. Clinically, inferior prognosis was observed with regard to age (<18 years), intracranial location, high grade ependymomas, and incomplete resection. We found that nucleolin was an unfavorable prognostic predictor for ependymomas. Moreover, our findings show a subset of aggravating outcomes in high-grade and posterior fossa tumors
3).

1977

One hundred and one patients with histologically confirmed ependymomas were studied over a 22-year period. Choroid plexus papilloma and subependymoma were not included. About half of the tumors were intracranial, with the majority of these infratentorial. The intraspinal tumors were equally divided between intramedullary and the “cauda” group. The majority of the intracranial tumors occurred in children, while almost all the intraspinal tumors were in adults. The histologic classification consisted of “typical ependymoma” (cellular, papillary and myxopapillary patterns) and “anaplastic ependymoma”. The intracranial and intramedullary tumors showed a predominantly cellular pattern, while the myxopapillary type was found only in the “cauda” group. The histology seems to be of limited value in assessing the prognosis in an individual patient with ependymoma. The postoperative prognosis was poor in the intracranial tumors, although radiotherapy increased the survival time without affecting the eventual fatal outcome. The prognosis in the intraspinal group was much better, with three-fourths of the patients living for at least 10 years. No patient with an anaplastic tumor survived for more than 6 years
4).